The purpose of the proposed supplement is to investigate the effects of smoking cessation alone and in conjunction with a program of structured physical activity on macromolecule oxidation caused by the generation of reactive oxygen species (ROS). Production of ROS in quantities that overwhelm the endogenous antioxidant defense system has been referred to as oxidative stress. An increasing body of evidence implicates oxidative stress in the pathogenesis of numerous diseases, including diabetes, cancer, and cardiovascular disease (CVD). Cigarette smoking exacerbates ROS formation and poses a significant oxidant stress in vivo. Both smoking cessation and structured physical activity programs have been independently reported to suppress ROS formation and have been suggested to help control disease onset and progression. To date, no study has determined the combined effect of these methods on ROS production and macromolecule oxidation. An ongoing clinical trial (R01 HL68569) presents a unique opportunity to efficiently and cost-effectively assess the combined effects of smoking cessation and physical activity on oxidative stress biomarkers. Specifically, we hypothesize that a smoking cessation intervention with an adjunctive exercise intervention will result in a greater attenuation in oxidative stress biomarkers than the same smoking cessation intervention without the exercise adjunct. Therefore, we propose the following specific aims: 1. To sample 120 participants in this on-going clinical trial, in which sedentary or minimally active cigarette smokers are randomized to one of two treatment arms: either a validated, cost-effective smoking cessation program plus a community-based exercise intervention, or the same smoking cessation program plus a contact time control wellness intervention); and, 2. To determine the efficacy of these two interventions to suppress oxidative stress at a 6-month follow-up compared to baseline measures. The primary dependent variables of the trial are serum DNA oxidation, plasma lipid peroxidation, plasma protein oxidation, and plasma antioxidant reducing capacity. The proposed investigation will be the first to study the role of smoking cessation and regular exercise to suppress oxidative stress. With approximately 23% of U.S. adults still smoking, and the role of oxidative stress in disease becoming increasingly more recognized, attempts to identify interventions aimed at suppressing oxidative stress in smokers are needed. As such, this study has substantial public health utility. [unreadable] [unreadable] [unreadable]